Chronic pathologic features after bilateral cortical impact in swine that do or do not develop post-traumatic epilepsy
Embargo Date
2028-02-21
OA Version
Citation
Abstract
Post-traumatic epilepsy (PTE) is one of the most detrimental sequelae of traumatic brain injuries (TBI) due to its refractory nature to antiepileptic drugs, making it extremely difficult to treat. PTE is classified as unprovoked seizures taking place at least one-week post-TBI. The mechanisms of why certain individuals develop PTE after TBI are not well understood. This study evaluates the chronic histopathological processes that occur in pigs that do or do not develop PTE post-TBI. Yucatan, male pigs (5 months old) received a bilateral cortical impact (n=10) or sham surgery (n=3). Post-injury, 6 of the 13 pigs developed PTE 20.8 weeks ± 6.3 weeks. Alcian blue stain indicated high density of sulfated glycosaminoglycans in the white matter tracts and subcortical white matter in pigs with and without PTE. Collagen Type Ⅰ did not increase in the injured cortex of any of the treatment groups. IBA-1 positive cells displayed significant, p < 0.16, upregulation in the percentage of microglia and macrophages present in the white matter of the injured cortex of pigs with TBI and PTE. Only pigs with PTE showed a specific pattern of positive hyperphosphorylated tau cells that consisted of a primarily neuronal profile that accumulated in the gray-white matter interface right below the sulci. T cells (CD3) and antigen-presenting macrophages or B cells (CD80) were not present after chronic TBI. These results signify that ongoing microglial activation and white matter injury could be quintessential biomarkers of epilepsy, which future studies may be able to use in the development of future therapeutic targets.
Description
2025